食欲素受体基因多态性与抗精神病药物所致体重增加的关联。
Association of orexin receptor polymorphisms with antipsychotic-induced weight gain.
作者信息
Tiwari Arun K, Brandl Eva J, Zai Clement C, Goncalves Vanessa F, Chowdhury Nabilah I, Freeman Natalie, Lieberman Jeffrey A, Meltzer Herbert Y, Kennedy James L, Müller Daniel J
机构信息
a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .
b Department of Psychiatry and Psychotherapy, Campus Mitte , Charité Universitätsmedizin Berlin , Berlin , Germany .
出版信息
World J Biol Psychiatry. 2016 Apr;17(3):221-9. doi: 10.3109/15622975.2015.1076173. Epub 2015 Oct 8.
OBJECTIVES
Antipsychotic-induced weight gain (AIWG) is a common side effect of treatment with antipsychotics such as clozapine and olanzapine. The orexin gene and its receptors are expressed in the hypothalamus and have been associated with maintenance of energy homeostasis. In this study, we have analysed tagging single nucleotide polymorphisms (SNPs) in orexin receptors 1 and 2 (HCRTR1 and HCRTR2) for association with AIWG.
METHODS
Schizophrenia or schizoaffective disorder subjects (n = 218), treated mostly with clozapine and olanzapine for up to 14 weeks, were included. Replication was conducted in a subset of CATIE samples (n = 122) treated with either olanzapine or risperidone for up to 190 days. Association between SNPs and AIWG was assessed using analysis of covariance (ANCOVA) with baseline weight and duration of treatment as covariates.
RESULTS
Several SNPs in HCRTR2 were nominally associated with AIWG in patients of European ancestry treated with either clozapine or olanzapine (P<0.05). In the replication analysis two SNPs rs3134701 (P = 0.043) and rs12662510 (P = 0.012) were nominally associated with AIWG. None of the SNPs in HCRTR1 were associated with AIWG.
CONCLUSION
This study provides preliminary evidence supporting the role of HCRTR2 in AIWG. However, these results need to be confirmed in large study samples.
目的
抗精神病药物所致体重增加（AIWG）是使用氯氮平、奥氮平等抗精神病药物治疗时常见的副作用。食欲素基因及其受体在下丘脑中表达，且与能量稳态的维持有关。在本研究中，我们分析了食欲素受体1和2（HCRTR1和HCRTR2）中的标签单核苷酸多态性（SNP）与AIWG的相关性。
方法
纳入了主要使用氯氮平和奥氮平治疗长达14周的精神分裂症或分裂情感性障碍患者（n = 218）。在接受奥氮平或利培酮治疗长达190天的CATIE样本子集（n = 122）中进行重复验证。使用协方差分析（ANCOVA）评估SNP与AIWG之间的相关性，将基线体重和治疗持续时间作为协变量。
结果
在使用氯氮平或奥氮平治疗的欧洲血统患者中，HCRTR2中的几个SNP与AIWG存在名义上的相关性（P<0.05）。在重复分析中，两个SNP rs3134701（P = 0.043）和rs12662510（P = 0.012）与AIWG存在名义上的相关性。HCRTR1中的SNP均与AIWG无关。
结论
本研究提供了初步证据支持HCRTR2在AIWG中的作用。然而，这些结果需要在大型研究样本中得到证实。
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